Chemoprevention of spontaneous tumorigenesis in p53-knockout mice.

Spontaneous tumorigenesis was evaluated in male p53-knockout (p53-/-) mice treated with dehydroepiandrosterone (DHEA), quercetin, d-limonene, or all-trans retinoic acid to determine whether tumor development in these mice can be modulated by cancer-chemopreventive agents. DHEA-treated mice experienced a delay in tumorigenesis (particularly lymphomas) and subsequent mortality (P < 0.01) relative to untreated control mice. Quercetin, d-limonene, and all-trans retinoic acid each had no effect on spontaneous tumor development in p53-/- mice. These data demonstrate that tumor development in p53-/- mice can be delayed by DHEA and suggest that p53-/- mice provide a useful model for evaluating strategies to offset the increased risk of tumorigenesis resulting from loss of p53 tumor suppressor function.